The Statistical Fragility of Platelet-Rich Plasma as Treatment for Chronic Noninsertional Achilles Tendinopathy: A Systematic Review and Meta-analysis

Abstract

Background: Randomized controlled trial (RCT) outcomes reaching statistical significance, frequently determined by P <.05, are often used to guide decision making. Noted lack of reproducibility of some RCTs has brought special attention to the limitations of this approach. In this meta-analysis, we assessed the robustness of RCTs evaluating platelet-rich plasma (PRP) for the treatment of chronic noninsertional Achilles tendinopathy (AT) by using fragility indices. Methods: The present study was a systematic review and meta-analysis of RCTs comparing outcomes after PRP injection vs alternative treatment in patients with AT. Representative data sets were generated for each reported continuous outcome event using summary statistics. Fragility indices refer to the minimal number of patients whose status would have to change from a nonevent to an event to turn a statistically significant result into a nonsignificant result, or vice versa. The fragility index (FI) and continuous FI (CFI) were determined for dichotomous and continuous outcomes, respectively, by manipulating each data set until reversal of significance (a=0.05) was achieved. The corresponding fragility quotient (FQ) and continuous FQ (CFQ) were calculated by dividing FI/CFI by sample size. Results: Of 432 studies screened, 8 studies (52 outcome events) were included in this analysis. The 12 dichotomous outcomes had a median FI of 4.5 (FQ: 0.111), and the 40 continuous outcomes had a median CFI of 5 (CFQ: 0.154). All 52 outcome events included lost-to-follow-up data, and 12 (23.1%) indicated a greater number of patients lost to follow-up than the FI or CFI. Conclusion: Our findings suggest that RCTs evaluating PRP for AT therapy lack statistical robustness, because changing only a small number of events may alter outcome significance. Level of Evidence: Level II, therapeutic study.

The Statistical Fragility of Trials Comparing Cervical Disc Arthroplasty and Anterior Cervical Discectomy and Fusion

“…The values for FIs in this analysis are consistent with previous fragility analyses within different orthopedic surgery subspecialties, which reported median FIs ranging from 2 to 5 with associated FQs ranging from 0.032 to 0.111. [34][35][36][37][38][39][40][41] This suggests that the RCT data for dichotomous outcomes comparing CDA versus ACDF are at least comparably robust to data from trials from other orthopedic subspecialties. However, the continuous fragility metrics from the present study cannot be directly compared these values as the CFI and FI are inherently different in their derivation.…”

“…Statistical Fragility of Continuous Outcomes in RCTs Evaluating CDA versus ACDF IQR: 1.9-13.3) for sports medicine and arthroscopy literature, Gupta et al 42 reported a median CFI of 6 (CFQ: 0.141) for 6 RCTs investigating intraoperative ketamine infusion during scoliosis surgery, and Xu et al34 reported a median CFI of 5 (CFQ: 0.154) for 8 RCTs evaluating platelet-rich plasma injection for Achilles tendinopathy. Ho43 …”

The impact of surgical randomised controlled trials on the management of FAI syndrome: a citation analysis

“…Few studies have utilised this methodology in the orthopaedic literature due to its recent introduction [44,57]. Nonetheless, the median CFI of trials comparing surgical vs. non-surgical management of FAIS (CFI = 19) is higher than values reported in prior orthopaedic studies including Ortiz-Babilonia et al's study on trials assessing the management of degenerative cervical pathology (median CFI = 14, IQR: 9-22) [44], and Xu et al's study on trials assessing the use of platelet-rich plasma in the management of chronic non-insertional Achilles tendinopathy (median CFI = 5, IQR: 3.5-9) [57]. The trend of FAIS trials being less fragile than other orthopaedic trials is no longer present when studies assessing either minor or major variations in surgical techniques are included (median CFI = 4.8; range 1-32.2).…”

Treatment of skin defects with PRP enriched with hyaluronic acid – histological aspects in rat model

“…PRP is a source of growth factors and, consequently, has mitotic, angiogenic, and chemotactic properties, representing an adjuvant treatment alternative for acute and chronic wounds. Furthermore, the application of PRP has been shown to be effective not only in the repair of soft tissues [ 24 , 25 ], but also in bone and cartilage reconstruction, tendons [ 26 , 27 , 28 , 29 ], hair growth, etc. The addition of bioactive excipients, such as HA, appears to accelerate endothelial, epithelial, and epidermal regeneration of PRP [ 30 , 31 ].…”